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Kidney fibrosis constitutes the shared final pathway of nearly all chronic nephropathies, but biomarkers for the non-invasive assessment of kidney fibrosis are currently not available. To address this, we characterize five candidate biomarkers of kidney fibrosis: Cadherin-11 (CDH11), Sparc-related modular calcium binding protein-2 (SMOC2), Pigment epithelium-derived factor (PEDF), Matrix-Gla protein, and Thrombospondin-2. Gene expression profiles in single-cell and single-nucleus RNA-sequencing (sc/snRNA-seq) datasets from rodent models of fibrosis and human chronic kidney disease (CKD) were explored, and Luminex-based assays for each biomarker were developed. Plasma and urine biomarker levels were measured using independent prospective cohorts of CKD: the Boston Kidney Biopsy Cohort, a cohort of individuals with biopsy-confirmed semiquantitative assessment of kidney fibrosis, and the Seattle Kidney Study, a cohort of patients with common forms of CKD. Ordinal logistic regression and Cox proportional hazards regression models were used to test associations of biomarkers with interstitial fibrosis and tubular atrophy and progression to end-stage kidney disease and death, respectively. Sc/snRNA-seq data confirmed cell-specific expression of biomarker genes in fibroblasts. After multivariable adjustment, higher levels of plasma CDH11, SMOC2, and PEDF and urinary CDH11 and PEDF were significantly associated with increasing severity of interstitial fibrosis and tubular atrophy in the Boston Kidney Biopsy Cohort. In both cohorts, higher levels of plasma and urinary SMOC2 and urinary CDH11 were independently associated with progression to end-stage kidney disease. Higher levels of urinary PEDF associated with end-stage kidney disease in the Seattle Kidney Study, with a similar signal in the Boston Kidney Biopsy Cohort, although the latter narrowly missed statistical significance. Thus, we identified CDH11, SMOC2, and PEDF as promising non-invasive biomarkers of kidney fibrosis.

Background and objectives Native kidney biopsies are commonly performed in the diagnosis of acute kidney diseases and CKD. Because of the invasive nature of the procedure, bleeding-related complications are not uncommon. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases–sponsored Kidney Precision Medicine Project requires that all participants undergo a kidney biopsy; therefore, the objective of this analysis was to study complication rates of native kidney biopsies performed using automated devices under kidney imaging. Design, setting, participants, & measurements This is a systematic review and meta-analysis of the literature published from January 1983 to March 2018. The initial PubMed search yielded 1139 manuscripts. Using predetermined selection criteria, 87 manuscripts were included in the final analysis. A random effects meta-analysis for proportions was used to obtain combined estimates of complication rates. Freeman–Tukey double-arcsine transformations were used to stabilize variance as complications were rare. Results A total of 118,064 biopsies were included in this study. Patient age ranged from 30 to 79 years, and 45% of patients were women. On the basis of our meta-analysis, pain at the site of biopsy is estimated to occur in 4.3% of biopsied patients, hematomas are estimated to occur in 11%, macroscopic hematuria is estimated to occur in 3.5%, bleeding requiring blood transfusions is estimated to occur in 1.6%, and interventions to stop bleeding are estimated to occur in only 0.3%. Death attributed to native kidney biopsy was a rare event, occurring only in an estimated 0.06% of all biopsies but only 0.03% of outpatient biopsies. Complication rates were higher in hospitalized patients and in those with acute kidney disease. The reported complications varied on the basis of study type and geographic location. Conclusions Although the native kidney biopsy is an invasive diagnostic procedure, the rates of bleeding complications are low. Albeit rare, death can occur postbiopsy. Complications are more frequently seen after kidney biopsies of hospitalized patients with AKI.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are common, heterogeneous, and morbid diseases. Mechanistic characterization of CKD and AKI in patients may facilitate a precision medicine approach to prevention, diagnosis, and treatment. The Kidney Precision Medicine Project aims to ethically and safely obtain kidney biopsies from participants with CKD or AKI, create a reference kidney atlas, and characterize disease subgroups to stratify patients based on molecular features of disease, clinical characteristics, and associated outcomes. An additional aim is to identify critical cells, pathways, and targets for novel therapies and preventive strategies. This project is a multicenter prospective cohort study of adults with CKD or AKI who undergo a protocol kidney biopsy for research purposes. This investigation focuses on kidney diseases that are most prevalent and therefore substantially burden the public health, including CKD attributed to diabetes or hypertension and AKI attributed to ischemic and toxic injuries. Reference kidney tissues (for example, living kidney donor biopsies) will also be evaluated. Traditional and digital pathology will be combined with transcriptomic, proteomic, and metabolomics analysis of the kidney tissue as well as deep clinical phenotyping for supervised and unsupervised subgroup analysis and systems biology analysis. Participants will be followed prospectively for ten years to ascertain clinical outcomes. Cell types, locations, and functions will be characterized in health and disease in an open, searchable, online kidney tissue atlas. All data from the Kidney Precision Medicine Project will be made readily available for broad use by scientists, clinicians, and patients.

BackgroundIn many European hospitals, ampicillin-resistant Enterococcus faecium (ARE) is endemic, while outbreaks of vancomycin-resistant E. faecium (VRE), belonging to the same genetic lineage, are increasingly reported. We studied the attributable mortality due to vancomycin resistance in patients with E. faecium bacteremia and evaluated whether this is mediated by a delay in appropriate antibiotic therapy.MethodsIn a retrospective matched cohort study, patients with VRE bacteremia occurring between 2009 and 2014 in 20 Dutch and Danish hospitals were matched to patients with ARE bacteremia, on hospital, ward, length of hospital stay prior to bacteremia, and age. The risk ratio (RR) for 30-day mortality contrasting VRE with ARE was estimated with further analytic control for confounding factors.ResultsIn all, 63 VRE and 234 ARE episodes were matched (36 and 130 for the Netherlands and 27 and 104 for Denmark). Crude 30-day mortality was 27% and 38% for ARE in the Netherlands and Denmark, respectively, and 33% and 48% for VRE in the respective countries. The adjusted RR for 30-day mortality for VRE was 1.54 (95% confidence interval (CI) 1.06-2.25). Although appropriate therapy was initiated later for VRE than for ARE bacteremia, this did not appear to mediate the increased mortality risk.ConclusionsCompared to ARE bacteremia, VRE bacteremia was associated with higher 30-day mortality. One explanation for this association would be increased virulence of VRE, although both phenotypes belong to the same well-characterized core genomic lineage. Alternatively, it may be the result of unmeasured confounding.

Pegylated liposomal doxorubicin (PLD) is used as a second-line therapy for gynecologic cancers, with a better short-term toxicity profile compared to doxorubicin or other anthracyclines. We screened 14 patients with recurrent gynecologic cancers, who underwent prolonged treatment with large cumulative doses of PLD for overt or subtle signs of cardiotoxicity (CTX) using standard and advanced echocardiography techniques [3D volumetric method for left ventricular ejection fraction (LVEF) and left ventricular/right ventricular global longitudinal strain]. Half the patients had previous echocardiographic studies available for comparison. The average PLD treatment duration was 23.6 ± 10.8 months (range 13–57), accumulating dose of 1387 ± 483 mg (range 780–2538 mg). The study group had a normal LVEF both by 2D-echo (60 ± 5%, range 50–67) and 3D echo (58 ± 5%, range 46–63). Two patients (14%) were found to have minimally reduced ejection fraction by 2D and 3D echo (50%/46% and 51%/49%, respectively) that did not meet the current definition of CTX. For the seven patients who had consecutive echocardiography studies, the average LVEF remained stable between studies (59 ± 7, 60 ± 9 and 58 ± 10.5% for the latest study, previous, p

ZusammenfassungDie hereditären periodischen Fiebersyndrome sind durch periodisch auftretende muskuloskelettale Symptome und stark erhöhte Serumspiegel von C-reaktivem Protein und Serum-Amyloid-A charakterisiert. Das familiäre Mittelmeerfieber wird zumeist bei Patienten mit türkisch-armenischer Herkunft diagnostiziert und mit Colchicum behandelt. Bei Unwirksamkeit von Colchicum oder Kontraindikationen gegen Colchicum kann eine Therapie mit Anakinra oder anderen gegen Interleukin-1 gerichteten Medikamenten erfolgen. Genetische Mutationen können auch bei Patienten ohne positive Familienanamnese nachgewiesen werden, da die Eltern asymptomatische Träger einer autosomal rezessiven Erkrankung sein können. Andere Fiebersyndrome wie TRAPS, CAPS und HIDS müssen abgegrenzt werden, da eine Therapie mit Colchicum bei diesen Erkrankungen unwirksam ist. Das Risiko für eine Amyloidose ist bei allen unbehandelten periodischen Fiebersyndromen deutlich erhöht. Die AA-Amyloidose beginnt mit einer Mikroalbuminurie und führt ohne Therapie zu einem nephrotischen Syndrom und einer terminalen Niereninsuffizienz. Das Amyloidoserisiko kann nur durch eine suffiziente Kontrolle der systemischen Entzündung minimiert werden.

Diagnosis of chronic Q fever is difficult. PCR and culture lack sensitivity; hence, diagnosis relies mainly on serologic tests using an immunofluorescence assay (IFA). Optimal phase I IgG cutoff titers are debated but are estimated to be between 1:800 and 1:1,600. In patients with proven, probable, or possible chronic Q fever, we studied phase I IgG antibody titers at the time of positive blood PCR, at diagnosis, and at peak levels during chronic Q fever. We evaluated 200 patients, of whom 93 (46.5%) had proven, 51 (25.5%) had probable, and 56 (28.0%) had possible chronic Q fever. Sixty-five percent of proven cases had positiveCoxiella burnetiiPCR results for blood, which was associated with high phase I IgG. Median phase I IgG titers at diagnosis and peak titers in patients with proven chronic Q fever were significantly higher than those for patients with probable and possible chronic Q fever. The positive predictive values for proven chronic Q fever, compared to possible chronic Q fever, at titers 1:1,024, 1:2,048, 1:4,096, and ≥1:8,192 were 62.2%, 66.7%, 76.5%, and ≥86.2%, respectively. However, sensitivity dropped to 1:1,024 is not recommended due to increased false-negative findings (sensitivity < 60%) and the high morbidity and mortality of untreated chronic Q fever. Our study emphasizes that serologic results are not diagnostic on their own but should always be interpreted in combination with clinical parameters.

AA amyloidosis can be the consequence of any chronic inflammatory disorder. It is most commonly associated with chronic inflammatory rheumatic, pulmonary or gastrointestinal diseases, familial Mediterranean fever or other rare periodic syndromes. AA amyloidosis often affects the kidneys, gastrointestinal tract and the heart. Effective therapy of the underlying disease can normalize the inflammatory reaction and can slow or inhibit the deterioration of organ function if the diagnosis is made at an early stage of the disease. In rheumatoid diseases and in some periodic syndromes the use of antibodies against TNFalpha or IL-1 beta might be helpful. Patients with familial Mediterranean fever should regularly take colchicine to prevent attacks and to reduce the risk for development or progression of AA amyloidosis. Eprodisate is currently being investigated for AA amyloidosis and renal involvement.

A 29-year-old male patient with chronic hepatitis C infection and interferon alpha therapy in his medical history was admitted to the hospital because of the clinical manifestation of a pulmonary renal syndrome. High titers of proteinase-3-ANCA were detected, while an infectious agent was ruled out. After diagnosis of Wegener's granulomatosis the patient received prednisolone and cyclophosphamide pulse therapy and remission developed rapidly. Chronic hepatitis C infection as well as interferon therapy are frequently associated with autoimmune disorders. We assume that the interferon therapy itself has triggered autoimmune processes resulting in Wegener's granulomatosis in our patient. Thus we recommend to search specifically for autoimmune disorders in the past medical history and if necessary to consider a screening for autoantibodies before starting an interferon therapy. An autoimmune disease should also be taken into account if new symptoms develop under an ongoing interferon alpha therapy.

Crop workers are at high risk of heat-related illness (HRI) from internal heat generated by heavy physical work, particularly when laboring in hot and humid conditions. The aim of this study was to identify risk factors for HRI symptoms in Washington crop workers using an audio computer-assisted self-interview (A-CASI) instrument that has undergone reliability and validity evaluation. A cross-sectional A-CASI survey of 97 crop workers in Washington State was conducted during the summer of 2013. Potential HRI risk factors in demographic, training, work, hydration, clothing, health, and environmental domains were selected a priori for evaluation. Mixed-effects logistic regression was used to identify risk factors for self-reported symptoms associated with heat strain and HRI (dizziness/light-headedness or heavy sweating) experienced at work in hot conditions. An increase in age was associated with a lower odds of HRI symptoms (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.87-0.98). Piece rate compared with hourly payment (OR = 6.20; 95% CI = 1.11-34.54) and needing to walk for more than 3 minutes to get to the toilet, compared with less than 3 minutes (OR = 4.86; 95% CI = 1.18-20.06), were associated with a higher odds of HRI symptoms. In this descriptive study of risk factors for HRI symptoms in Washington crop workers, decreased age (and less work experience), piece rate pay, and longer distance to the toilet were associated with self-reported HRI symptoms. Modifiable workplace factors should be considered in HRI prevention efforts that are evaluated using objective measures in representative working populations.

The aim of this study was to estimate the 1-year prevalence of headache, migraine, tension-type headache (TTH) and chronic daily headache (CDH), and the degree of association of migraine with some sociodemographic characteristics of the population of Florianopolis, Brazil. This is a cross-sectional, door-to-door, population-based study. In 300 randomly selected households, 625 subjects, aged 15–64 years, responded to a structured questionnaire. The 1-year prevalence of headache was 80.8%, of migraine 22.1%, of TTH 22.9%, and of CDH 6.4%. Migraine and CDH were significantly more prevalent in females than in males. Migraine was significantly associated with the following variables: low household income, low electricity consumption, and divorced or widowed marital status. We have shown high prevalences of migraine and CDH in Florianopolis, close to the higher rates of previous studies. There was a preponderance of migraine in females, divorced or widowed, with a low socioeconomic level.

Objective To evaluate the ability of a quantified pp65-antigenemia assay to predict the development of human cytomegalovirus (HCMV) disease in patients with an advanced HIV infection. Design A prospective longitudinal study between March 1993 and December 1996. Blood samples for the pp65-antigenemia assay were drawn at 2-3 month intervals. Setting AIDS department of an institutional tertiary care centre. Patients A total of 101 HIV-infected patients with CD4 lymphocyte counts of 100/mm3 or less were enrolled. Ninety-seven patients were eligible for analysis. All patients gave informed consent. Main outcome measures The development of HCMV disease. Results Of the 97 patients, 24 developed HCMV disease after a median follow-up of 10.6 months. Three months before the development of HCMV disease, an increase in the median number of pp65-antigen-positive leukocytes was observed. The highest combination of sensitivity (45%) and specificity (94%) for the development of HCMV disease within the next 3 months was found when an assay cut-off level of 48/10(5) pp65-antigen-positive leukocytes was applied, with a positive predictive value (PPV) for the development of HCMV disease of 75%. The Kaplan-Meier estimate of HCMV disease-free survival after patients reached 48/10(5) or more antigen-positive leukocytes on longitudinal follow-up was a median 3.7 months [95% confidence interval (CI), 2.5-8.5]. The hazard ratio (HR) of this threshold level for the development of HCMV disease was 9.6 (95% CI, 4.2-21.8). Conclusion Longitudinal follow-up using the pp65-antigenemia assay of HIV-infected patients with a low CD4 lymphocyte count improves the identification of patients who will develop HCMV disease in the foreseeable future, and should be considered for the selection of patients who may benefit from pre-emptive HCMV treatment.

This retrospective study was performed to determine if the chest radiograph could serve as a predictor for acute lung rejection in heart-lung transplantation patients. The findings on chest radiographs were correlated with the results of transbronchial biopsies in 16 heart-lung transplantation patients. The chest radiographs immediately preceding 83 biopsies were evaluated for a variety of findings. The histopathologic results of the lung biopsies were divided into five categories: (1) acute lung rejection (n = 25); (2) suggestive, but not diagnostic, of acute lung rejection (n = 8); (3) nonspecific (n = 26); (4) infection (n = 17); and (5) normal lung (n = 9). Biopsies from two patients showed both acute lung rejection and cytomegalovirus infection and were included in both categories. These histopathologic results were then correlated with the radiologic observations. We found that the combination of septal lines and new or increasing pleural effusions, without concomitant increase in cardiac size or vascular pedicle width, or evidence of vascular redistribution, indicated acute lung rejection with a sensitivity of 68% (17/25), specificity of 90% (52/58), and overall accuracy of 83% (69/83). We conclude that the chest radiograph is a useful indicator of acute lung rejection.

Two hundred seventy-four computed tomographic (CT) scans of the thorax were obtained in 209 patients with malignant lymphoma (153 Hodgkin disease and 56 non-Hodgkin lymphoma). Fourteen patients (6.6%) were shown to have adenopathy involving the cardiophrenic angle lymph nodes on CT. Of these, only three were considered positive on the basis of chest radiography alone. The anatomy of these diaphragmatic lymph nodes and CT appearance of these nodes when pathologically enlarged are discussed.

A preliminary study was used to test the strengths and weaknesses of our dual energy radiography system as applied to study of chest lesions. Six patients had a pulmonary nodule or pulmonary nodules known to be present on the basis of prior chest films substantiated by full lung tomograms or CT scans of the chest. The results of the dual energy studies as compared to the chest film findings and the other special studies are reported.© (1981) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.